Since the first evidence for the phosphomannosyl recognition on acid hydrolases appeared (Kaplan et al., Proc. Natl. Acad. Sci. 74, 2026, 1977) its structure has been verified, its receptor has been purified, and its biosynthesis has been partially elucidiated. Information about this recognition system may be useful for the development of enzyme replacement therapy, the characterization of the genetic defect in I cell disease, and the elucidation of the mechanisms of lysosome biogenesis. Here we outline plans for the analysis of the effects of a mutation on the interaction of the marker with the receptor, the evaluation of the content and distribution of protein bearing the marker in human fibroblasts, and the correlation of marker pool sizes with rates of secretion and enzyme packaging into lysosomes. We also describe efforts to demonstrate, characterize, and purify the recognition marker synthetase. Finally we discuss efforts to determine if the marker is a general feature of glycoprotein processing intermediates.